Next-generation imaging to interrogate biological systems across time and space

The University of North Carolina at Chapel Hill received a $2,257,345 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) for the period September 1, 2025 through August 31, 2029. The award supports the development of next-generation microscopy instrumentation and computational methods to advance biological research across spatiotemporal scales. The project will combine novel optical principles with computer vision to create autonomous microscopes capable of real-time data processing and adaptive navigation through biological specimens based on experimental objectives, addressing the critical challenge of translating rapid data generation into meaningful biological insights.

In parallel research initiatives, the award funds application of advanced light sheet and single-molecule imaging techniques to investigate how proteins function within cellular nuclei. Specifically, the research will examine how thousands of distinct proteins navigate within the nucleus and execute specialized biological functions, with the ultimate goal of understanding how functional environments are organized at the individual cell level. The deliverables include both instrumental innovations in microscopy capabilities and fundamental discoveries regarding nuclear protein organization and function that will enable future biological studies across multiple research domains.

Abstract

Our research develops new microscopes that transform our ability to observe biological specimens and applies these microscopes to solve fundamental problems in cell biology. Light microscopes are a cornerstone of biological research. Recent optical, technological, and computational advances have greatly increased the resolution and speed at which we can observe living samples. However, in many cases, the ability of instruments to generate data has greatly outpaced our ability to analyze, interpret, and act upon this information. This is especially true for microscopes that can image across spatiotemporal scales, observing single molecules to whole organisms. Over the next five years, we will combine new optical principles together with computer vision to build autonomous microscopes that can not only capture data more rapidly, but also more efficiently. These instruments will be able to process data in real time and use this information to navigate through and interact with biological specimens based on experimental goals. In parallel projects, we will leverage recent advances in light sheet and single molecule imaging to study a key biological question, namely, how thousands of unique proteins navigate within and accomplish distinct biological functions in the cell nucleus. The overall vision for this research is to develop new microscope capabilities that enable new studies of biological processes and to test key hypotheses about how functional environments are organized in the nucleus of individual cells.